A compound represented by the formula (VI-a) (hereinafter referred to as compound (VI-a)): wherein R1 represents a hydrogen atom or an alkali metal, or a lactone form of compound (VI-a) represented by the formula (VI-b) (hereinafter referred to as compound (VI-b)): is known to inhibit HMG-CoA reductase and exhibit an action of reducing serum cholesterol and the like (The Journal of Antibiotics, 29, 1346 (1976)).
There have been several reports regarding a method for producing the compound (VI-a) or the compound (VI-b) from a compound represented by the formula (V-a) (hereinafter referred to as compound (V-a)): wherein R1 represents a hydrogen atom or an alkali metal, or the lactone form of compound (V-a) represented by the formula (V-b) (hereinafter referred to as compound (V-b)): using a microorganism.
Specifically, Japanese Patent Application Laid-Open (kokai) No. 57-50894 describes a method which uses filamentous fungi; both Japanese Patent Application Laid-Open (kokai) No. 7-184670 and International Publication WO96/40863 describe a method which uses Actinomycetes; and Japanese Patent No. 2672551 describes a method which uses recombinant Actinomycetes. As is well known, however, since filamentous fungi and Actinomycetes grow with filamentous form by elongating hyphae, the viscosity of the culture in a fermentor increases. This often causes shortage of oxygen in the culture, and since the culture becomes heterogeneous, reaction efficiency tends to be reduced. In order to resolve this oxygen shortage and maintain homogeneousness of the culture, the agitation rate of the fermentor should be raised, but by raising the agitation rate, hyphae are sheared and activity of the microorganisms tends to decrease (Basic Fermentation Engineering (Hakko Kogaku no Kiso) p. 169-190, P. F. Stansbury, A. Whitaker, Japan Scientific Societies Press (1988)).
Furthermore, the above Actinomycetes and filamentous fungi have an ability to sporulate. Since spores tend to disperse much more easily than cells and have an ability of surviving even under conditions where vegetative cells perish readily, these spores tend to become a source of microorganism contamination in culturing and purification processes.